Performing a pulmonary function test (PFT) generally involves the use of instrumentation operable to measure physiologic respiratory volume(s) and/or respiratory gas exchange. PFT instruments (also referred to herein as PFT equipment or devices) can include testing capability for dynamic lung volumes, static and/or absolute lung volumes (and related parameters) using washout, dilution, and/or plethysmographic methods, and/or measures of gas exchange such as calculated transfer factor (DLCO) and related primary measured parameters and related physiologic tests. Spirometry parameters are typically measured with gas flow sensors using a variety of technologies. In the case of washout techniques, static and absolute lung volume parameters are typically measured with gas analyzers measuring inhaled and exhaled CO2 and O2 gas concentrations in conjunction with the aforementioned gas flow measurements.
Plethysmographic methods of measuring static and absolute lung volume parameters typically utilize flow and pressure sensors. Calculation of gas exchange parameters are based on gas analyzer measurements of inhaled and exhaled CO and a non-diffusing tracer gas, such as CH4 or He, in conjunction with the aforementioned gas flow measurements. Commercially available PFT instruments used for static lung volume and/or gas exchange measurements typically provide a test gas from a high-pressure source that is regulated to atmospheric pressure for delivery to patients using a regulator (e.g., a demand valve).
To assure accurate and/or precise measurements, it is desirable to verify and/or calibrate PFT instruments periodically and/or prior to patient use. Such verification and/or calibration can serve to confirm, for example, that the PFT instrument conforms to the stated manufacturer's performance specifications. The present application relates generally to a means and apparatus to verify and/or calibrate a PFT instrument to its stated manufacturer's specifications in a clinical environment.
Verifying PFT instrumentation generally refers to subjecting the instrument to a known standard, reference volume, and/or known standard, reference concentration, of test gases, including air at ambient temperature and pressure, and verifying that the PFT equipment returns a value consistent with the known volume reference and/or known gas concentration reference.
Calibrating PFT instrumentation generally refers to adjusting parameters of the PFT instrument in response to subjecting the PFT instrument to a known standard volume and/or known standard concentrations of a test gases such that the PFT instrument returns a value consistent with the known volume and/or gas concentration. Commonly available PFT instruments are typically calibrated at the time of manufacture and/or by trained service technicians and verified by end-users and/or medical professionals under normal operating conditions in the patient testing environment.
It is further desirable for PFT instruments to verifiably provide physiologically and/or clinically representative data. To verify that PFT instruments have sufficient accuracy and/or precision to provide physiologically representative and/or clinically meaningful data, it is desirable to calibrate and/or validate PFT instruments to minimum clinical accuracy requirements such as those set by peer societies, in particular the Joint American Thoracic Society and European Respiratory Society guidelines for the standardization of lung function testing in the patient testing (clinical) environments.
Generally, validation and/or calibration techniques applied to PFT instruments involves passing a known volume of gas and/or one or more gas mixtures having a known concentration or ratio of concentrations of a test gas to the PFT instrument. Existing methods for validating and/or calibrating PFT instruments include:                1. Utilizing a person with a known transfer capacity as a measurement reference.        2. Utilizing a device that delivers known gas volumes and/or at least two gas mixtures from individual sources having differing, but known, concentrations of a test gas.        3. Utilizing a device that delivers known gas volumes and at least two gas mixtures having known concentrations of the test gas by diluting one gas mixture into another. For example, U.S. Pat. No. 9,186,090, which is hereby incorporated by reference in its entirety, describes some methods and apparatus for diluting one gas mixture into another to validate and/or calibrate DLCO capable PFT equipment.Such methods are generally unable to calibrate and/or validate PFT instruments to minimum clinical standards and/or manufacturers' specifications, particularly in a clinical environment.        
Regarding spirometry measurements: current minimum clinical volume accuracy requirements of PFT instruments requires measured volumes be within +/−2% or 50 mL (whichever is greater) of expected over a volume range of 0.5 L to 8 L and within flow rates up to 14 L/Sec. The current industry standard volume reference used to verify PFT instruments in the field is a gas syringe that displaces relatively large volumes of gas, such as three to nine liters of gas. During verification or calibration procedures, the syringe is commonly subject to heating and cooling sources typically found in patient testing environments, such as HVAC, direct sunlight, or body heat from direct contact of a user. Consequently, using existing devices and practices, the volume delivered by the syringe deviates from its certified value to levels that render it insufficient to verify the manufacturer's specifications or minimal clinical accuracy requirements, whichever is better. For example, a temperature difference of as little as 3° C. between the gas temperature within the volume reference standard device and ambient gas temperature will introduce an error of approximately 1% into the reference volume.
Regarding absolute and static lung volume measurements utilizing nitrogen washout methods: current minimum clinical volume accuracy requirements of PFT instruments requires measured volume accuracies commensurate with spirometry as described above while delivering O2 test gas at atmospheric pressure to a patient. Accuracy of current volume reference standards are subject to the same limitations as described above. A further limitation is that existing volume reference standards do not provide a physiologically representative dynamic compliance as a load to the PFT instrument when inspiring test gas from a regulated high-pressure gas source, which can render the simulated PFT volume measurement invalid, regardless of its delivered volume accuracy.
Regarding gas exchange measurements: current minimum clinical volume accuracy requirements of PFT instruments measuring single-breath determination of carbon monoxide uptake in the lung (DLCO) are commensurate with the standards for absolute and static lung volume measurements as described above. In addition to the volume accuracy requirements, achieving the clinical accuracy requirements of the DLCO parameter (+/−2 mL/min/mmHg @2σ) requires gas analyzer measurements to be linear within +−0.75% of their full scale range. The gas analyzer linearity requirement applies to physiological ranges of use, which typically are 50% to 80% of full-scale concentration for the tracer gas (e.g., CH4 or He) and 30% to 50% of full-scale concentration of CO gas, subject to variations in field operating conditions as previously described. Typically, linearity of gas analyzers is validated and/or calibrated using several standard gases having different concentrations of the gas under test. Pre-mixed precision gas mixtures suitable for calibrating and/or validating gas analyzers with suitable accuracy to meet the manufacturer's specifications and/or clinical accuracy requirements of the DLCO parameter, are not, however, available and/or are extremely expensive.
Furthermore, reference standards (e.g., syringes) are generally unable to provide sufficiently accurate ratiometric gas concentrations to verify minimal gas analyzer linearity requirements, whether delivered by gas dilution methods or from methods utilizing multiple gas sources. For example, the mixing ratio of a dilution syringe can theoretically be indirectly determined by measuring relevant volumes of a dilution syringe with water and a suitable NIST traceable scale. However, the actual geometry and construction of dilution syringes can render such a theoretical approach unsatisfactory in practice. In particular, it can be challenging or impossible to eliminate air pockets from within the syringe, valve-less diffusion barriers have no defined boundary to water measure, and valve-based diffusion barriers may not be openable without disassembly or modification. Because of the deficiencies of currently existing standards and methods to calibrate and/or validate PFT instruments to manufacturers' specifications and/or minimum clinical standards in a clinical environment, a need for improved methods and devices for calibrating and/or validating PFT instruments is needed. Such improved methods and devices can be operable to produce PFT instruments with improved accuracy and/or precision.
Some methods and apparatus described herein may be suitable to calibrate and/or validate PFT devices according to at least manufacturer's specifications and/or current minimum clinical standards/requirements. Methods and apparatus described herein may also be suitable to calibrate and/or validate PFT equipment to levels of accuracy and/or precision beyond current minimum clinical standards/requirements and/or may be suitable to calibrate and/or validate PFT equipment under variable field operating conditions (including, for example, ambient temp changes of up to 15° C. and operator induced variability).